Role of Lipocalin-2 in Amyloid-Beta Oligomer-Induced Mouse Model of Alzheimer’s Disease
Abstract
:1. Introduction
2. Materials and Methods
2.1. Human Samples
2.2. Human Brain Autopsy
2.3. Animals
2.4. Oligomeric Amyloid-Beta Preparation and Infusion
2.5. Morris Water Maze
2.6. Enzyme-Linked Immunosorbent Assay (ELISA)
2.7. Tissue Collection and Sample Preparation
2.8. Immunohistochemistry Analysis
2.9. Analysis of Microglia Morphology
2.10. Immunofluorescence
2.11. Western Blotting
2.12. Statistical Analysis
3. Results
3.1. Serum LCN2, White Matter Ischemic Changes on Brain MRI, and LCN2 Expression in Human Frontal Cortex Are All Increased in AD Patients
3.2. AβO-Injected Mice Have Memory Impairment
3.3. Activated Microglia, Astrocyte, and Pro-Inflammatory Cytokines Are Increased in the Hippocampus of AD Mouse Model
3.4. The AD Mouse Model Exhibits Blood–Brain Barrier Leakage
3.5. Increased Expression of LCN2, MMP-9, and STAT-3 in the AD Mouse Model
3.6. Increased Iron Dysregulation and Oxidative Stress in AD Mouse Model
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Controls (n = 17) | Alzheimer’s Disease (n = 37) | p1-Value | p2-Value | |
---|---|---|---|---|
Age (years) | 71.8 ± 8.1 | 78.1 ± 6.4 | 0.003 | |
Sex (female:male) | 16:1 | 25:12 | 0.043 | |
Education (years) | 8.89 ± 4.27 | 6.69 ± 5.01 | 0.255 | |
HbA1C (%) | 5.6 ± 0.4 | 5.6 ± 0.3 | 0.525 | |
Hypertension (%) | 4 (23.5%) | 16 (43.2%) | 0.229 | |
K-MMSE | 27.6 ± 2.7 | 17.7 ± 4.7 | <0.001 | |
GDS | 2.1 ± 0.7 | 4.1 ± 0.8 | <0.001 | |
ApoE e4 genotype (%) | 2/13 (15.4%) | 11/24 (45.8%) | 0.083 | |
Folate (ng/mL) | 11.9 ± 5.0 | 7.1 ± 4.5 | 0.006 | 0.064 |
Vitamin B12 (pg/mL) | 1133.8 ± 538.2 | 876.9 ± 466.6 | 0.149 | 0.134 |
Homocysteine (µmol/L) | 7.7 ± 1.1 | 13.4 ± 3.9 | <0.001 | <0.001 |
LCN2 (ng/mL) | 42.1 ± 22.7 | 63.8 ± 31.8 | 0.018 | 0.147 |
BDNF (pg/mL) | 11.3 ± 3.7 | 12.5 ± 5.0 | 0.36 | 0.116 |
ARWMC (score) | 1.4 ± 2.0 | 3.5 ± 3.2 | 0.007 | 0.186 |
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Kang, H.; Shin, H.J.; An, H.S.; Jin, Z.; Lee, J.Y.; Lee, J.; Kim, K.E.; Jeong, E.A.; Choi, K.Y.; McLean, C.; et al. Role of Lipocalin-2 in Amyloid-Beta Oligomer-Induced Mouse Model of Alzheimer’s Disease. Antioxidants 2021, 10, 1657. https://doi.org/10.3390/antiox10111657
Kang H, Shin HJ, An HS, Jin Z, Lee JY, Lee J, Kim KE, Jeong EA, Choi KY, McLean C, et al. Role of Lipocalin-2 in Amyloid-Beta Oligomer-Induced Mouse Model of Alzheimer’s Disease. Antioxidants. 2021; 10(11):1657. https://doi.org/10.3390/antiox10111657
Chicago/Turabian StyleKang, Heeyoung, Hyun Joo Shin, Hyeong Seok An, Zhen Jin, Jong Youl Lee, Jaewoong Lee, Kyung Eun Kim, Eun Ae Jeong, Kyu Yeong Choi, Catriona McLean, and et al. 2021. "Role of Lipocalin-2 in Amyloid-Beta Oligomer-Induced Mouse Model of Alzheimer’s Disease" Antioxidants 10, no. 11: 1657. https://doi.org/10.3390/antiox10111657